The objective of this proposal is to characterize mechanisms whereby cell-mediated immune responses are regulated by activated thymus-derived lymphocytes and their soluble products. These studies will focus primarily upon suppression and amplification of murine immune responses in vitro utilizing mixed lymphocyte reactions and the generation of cytotoxic lymphocytes as essential assay systems. Lymphocyte subpopulations which mediate such activities will be fully characterized by physical properties, cell surface markers and physiologic characteristics, biologically active soluble products of such lymphocyte subpopulations will be identified and acharacterized biochemically and immunochemically. Genetic requirements for induction of regulatory activity and for the interaction among T cell subpopulations in expression of regulatory processes will be examined. Cell-mediated immune responses in vivo, particularly graft-vs-host reactions and delayed hypersensitivity, will also be studied to elucidate the role of activated T cells and T cell factors in control of physiologic immune responses. Finally, techniques recently developed for studying regulation of human responses in vitro will be exploited in an effort to extend studies in murine immunobiology to clinically important problems in regulation of immune responses. The proposal thus represents an extension of long-range commitments of this laboratory to explore fundamental problems in cellular immunology and, as feasible, to directly utilize new concepts developed in studies of human biology and disease.